title: Derlin-1 is overexpressed on the tumor cell surface and enables antibody-mediated tumor targeting therapy.
abstract: OBJECTIVE
  Tumor targeting therapy is one of the most promising strategies for anticancer treatment. Derlin-1 has been reported to participate in misfolded protein dislocation and integrates into the endoplasmic reticulum (ER) membrane to survey for such protein aggregates. We elucidate herein that Derlin-1 can leak to the plasmalemma from the ER in tumor cells and may have clinical application as a novel cancer target in the hope of developing a new tumor targeting therapy.
  
  
  METHODS
  The cell surface expression of Derlin-1 was shown by immunofluorescence analysis of nonpermeabilized cells and Western blotting of fractional proteins of tumor cells. Derlin-1 expression in cancerous tissues was also shown by immunohistochemistry. Biodistribution analysis and gamma-scintigraphic imaging were done using (125)I-labeled Derlin-1 targeting antibody in isogenic mice models. Finally, tumor-bearing mice were treated by the anti-Derlin-1 polyclonal antibody and monoclonal antibodies.
  
  
  RESULTS
  Derlin-1 was expressed on various tumor cell surfaces and adopted a homodimer conformation. Robust cytoplasmic and membrane expression of Derlin-1 was detected in various types of human cancers tissues but was not correlated with any clinicopathologic features of pancreatic cancer. Derlin-1 directed antibodies specifically targeted to colon tumors and significantly suppress tumor growth in isogenic mice.
  
  
  CONCLUSIONS
  These preclinical data show that Derlin-1 protein is a functional molecular target expressed on the tumor cell surface and is a candidate therapeutic target that may be translated into clinical applications.
authors.affiliation: Department of Cell and Molecular Biology, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, People's Republic of China.
authors.forename: Yuliang
authors.initials: Y
authors.lastname: Ran
authors.forename: Hai
authors.initials: H
authors.lastname: Hu
authors.forename: Dong
authors.initials: D
authors.lastname: Hu
authors.forename: Zhuan
authors.initials: Z
authors.lastname: Zhou
authors.forename: Yuemin
authors.initials: Y
authors.lastname: Sun
authors.forename: Long
authors.initials: L
authors.lastname: Yu
authors.forename: Lixin
authors.initials: L
authors.lastname: Sun
authors.forename: Jian
authors.initials: J
authors.lastname: Pan
authors.forename: Jun
authors.initials: J
authors.lastname: Liu
authors.forename: Tong
authors.initials: T
authors.lastname: Liu
authors.forename: Zhihua
authors.initials: Z
authors.lastname: Yang
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000627:therapeutic use*; D015153:Blotting, Western; D002462:Cell Membrane / Q000378:metabolism*; D049109:Cell Proliferation; D003593:Cytoplasm / Q000378:metabolism; D004721:Endoplasmic Reticulum / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism; D005260:Female; D005455:Fluorescent Antibody Technique; D006801:Humans; D018796:Immunoconjugates / Q000493:pharmacokinetics; D007457:Iodine Radioisotopes / Q000627:therapeutic use*; D008565:Membrane Proteins / Q000378:metabolism*; D051379:Mice; D008819:Mice, Nude; D009369:Neoplasms / Q000276:immunology / Q000378:metabolism* / Q000628:therapy*; D010446:Peptide Fragments / Q000276:immunology / Q000378:metabolism; D011817:Rabbits; D019275:Radiopharmaceuticals / Q000627:therapeutic use; D046888:Tissue Array Analysis; D014018:Tissue Distribution
chemical_list: D000911:Antibodies, Monoclonal; C487709:DERL1 protein, human; D018796:Immunoconjugates; D007457:Iodine Radioisotopes; D008565:Membrane Proteins; D010446:Peptide Fragments; D019275:Radiopharmaceuticals